Normal Lactate Research Articles

Pomalidomide Plus Low Dose Dexamethasone in Relapsed/Refractory Multiple Myeloma Patients: Results of the Real-World ‘Powerful’ Study

Pomalidomide Plus Low Dose Dexamethasone in Relapsed/Refractory Multiple Myeloma Patients: Results of the Real-World ‘Powerful’ Study

Microcirculation alterations in severe COVID-19 pneumonia.

PurposeTo assess the presence of sublingual microcirculatory and skin perfusion alterations in COVID-19 pneumonia.Materials and methodsThis is a preliminary report of a prospective observational study performed in four teaching intensive care units. We studied 27 mechanically ventilated patients with acute respiratory distress syndrome secondary to COVID-19. Sublingual microcirculation was assessed by hand-held videomicroscopy. A software-assisted analysis of videos was performed. We also measured capillary refill time.ResultsPatients were hemodynamically stable with normal lactate (1.8 [1.6–2.5] mmol/L) and high D-dimer (1.30 [0.58–2.93] μg/mL). Capillary refill time was prolonged (3.5 [3.0–5.0] s). Compared to previously reported normal values, total and perfused vascular density (21.9 ± 3.9 and 21.0 ± 3.5 mm/mm2) and heterogeneity flow index (0.91 ± 0.24) were high; and the proportion of perfused vessels (0.96 ± 0.03), microvascular flow index (2.79 ± 0.10), and red blood cell velocity (1124 ± 161 μm/s) were reduced. The proportion of perfused vessels was inversely correlated with total vascular density (Pearson r = −0.41, P = 0.03).ConclusionsCOVID-19 patients showed an altered tissue perfusion. Sublingual microcirculation was characterized by decreases in the proportion of perfused vessel and flow velocity along with high vascular densities. This last finding might be related to enhanced angiogenesis or hypoxia-induced capillary recruitment.

PROGNOSTIC VALUE OF PERSISTENTLY NORMAL LACTATE LEVELS IN PATIENTS WITH SHOCK

SESSION TITLE: Critical Care Posters SESSION TYPE: Original Investigation Posters PRESENTED ON: October 18-21, 2020 PURPOSE: Serum lactate levels are commonly used as markers of perfusion in the management of shock. However, several studies have shown that hyperlactatemia may not just be the result of hypoperfusion but also increased adrenergic stimulation. Based on these findings, some have postulated that persistently normal lactate levels in shock may represent a relative adrenergic deficiency. To our knowledge, no studies to date have evaluated outcomes in shock patients with persistently normal lactate levels. The purpose of this study is to compare all-cause mortality and severity of shock in patients with persistently normal serum lactate levels (lactate level <2.0 mmol/L for the first 6 hours during the treatment of shock) to those with elevated lactate levels (lactate level >2.0 mmol/L). METHODS: This is an IRB-approved, retrospective chart review of critically ill adult patients admitted to the intensive care unit (ICU) from December 2018 to November 2019 at NYU Langone Brooklyn. The inclusion criterion was the confirmed administration of catecholamine-based vasopressor therapy for at least 1 hour. Exclusion criteria included critical limb or mesenteric ischemia, documented chronic liver disease, epinephrine administration, metformin toxicity, confirmed seizure within 24 hours of vasopressor initiation, elevated alcohol level, or transition to comfort care. The primary endpoints were in-hospital and ICU mortality. Secondary endpoints included duration of therapy and the number of vasopressors required. Length of stay (LOS) and the need for organ support therapies were also evaluated. RESULTS: A total of 137 patients were analyzed (55 in normal lactate group and 82 in elevated lactate group). Overall, rates of ICU (36.6% vs 18.2%, p = 0.02) and in-hospital mortality (47.6% vs 30.1%, p=0.05) were higher in the elevated lactate group. This was despite there being no difference the duration of vasopressor therapy (29 vs 30 hours, p = 0.81) or the number of vasopressors required (1 vs 1, p = 0.211). In addition, there were no differences in the need for mechanical ventilation (37.8% vs 36.6%, p = 0.864), renal replacement therapy (7.3% vs 7.3%, p = 0.992), or hospital length of stay (10 vs 8 days, p = 0.142). CONCLUSIONS: Based on our findings, persistently normal lactate levels in shock appear to be associated with reduced all-cause mortality compared to those with elevated lactate levels. However, this does not appear to correlate with decreases in the duration of vasopressor therapy or the need for organ replacement therapies. CLINICAL IMPLICATIONS: Persistently normal lactate levels may represent good prognostic value as they appear to be associated with reduced mortality in critically ill patients with shock. However, without differences in vasopressor therapy duration or organ replacement therapy needs, it is unclear if elevated serum lactate levels are not simply the result of worsening end-organ perfusion. DISCLOSURES: No relevant relationships by Bhaskara Garimella, source=Web Response No relevant relationships by Vickie Kassapidis, source=Web Response No relevant relationships by John Kileci, source=Web Response No relevant relationships by Guillermo Munoz-Jurado, source=Web Response

ISCHEMIC COLITIS WITH NINTEDANIB USE: THE CONUNDRUM OF A COMMON SYMPTOM DUE TO A RARE CAUSE

SESSION TITLE: Fellows Diffuse Lung Disease Posters SESSION TYPE: Fellow Case Report Posters PRESENTED ON: October 18-21, 2020 INTRODUCTION: Most common adverse effects of Nintedanib are nausea, diarrhea, and liver dysfunction. Serious adverse events have been reported in approximately 30% of patients receiving Nintedanib treatment. We report a case of Nintedanib induced ischemic colitis in a patient with idiopathic pulmonary fibrosis. CASE PRESENTATION: An 84-year-old Caucasian Male with a past medical history significant for IPF presented to the Emergency Department with progressively worsening diffuse abdominal pain, anorexia, and diarrhea. He started taking Nintedanib 7 days before. Abdominal exam revealed rebound tenderness with guarding and rigidity. Laboratory evaluation showed an elevated leukocyte count and a normal lactate. Computed tomography scan of the abdomen demonstrated inflammatory changes and mildly dilated small bowel loops without any signs of obstruction. He underwent an urgent diagnostic laparoscopy for further evaluation. Procedure was converted to a laparotomy after he was noted to have ischemic bowel, with resection of the terminal ileum, cecum, and appendix. Pathology of resected specimen showed transmural ischemic necrosis of terminal ileum and cecum. Nintedanib was discontinued and he was discharged home in stable condition after an uneventful post-operative course. DISCUSSION: Nintedanib is a tyrosine kinase inhibitor that mediate elaboration of fibrogenic growth factors (eg, platelet-derived growth factor, vascular endothelial growth factor - VEGF, fibroblast growth factor). Nintedanib and its byproducts may cause direct intestinal mucosal damage. VEGF mediates release of nitric oxide, and its inhibition causes vasoconstriction. VEGFR inhibition significantly reduces the capillary network in intestinal villi. The WHO pharmaceutical newsletter showed disproportional reporting of colitis with Nintedanib use. Authors identified 10 cases of possible colitis from around the world. Pathology results were available in only 3/10 patients. Diarrhea and GI perforation are listed on Nintedanib’s prescribing label, while ischemic bowel (colitis) is not listed as an adverse event. CONCLUSIONS: Ischemic colitis can be a life-threatening condition if not detected early. It is important for health care providers to be aware of this complication when patients on Nintedanib who develop diarrhea, in the context of other abdominal complaints and findings. Reference #1: Kato M, Sasaki S, Nakamura T, et al. Gastrointestinal adverse effects of nintedanib and the associated risk factors in patients with idiopathic pulmonary fibrosis. Sci Rep. 2019;9(1):12062. Published 2019 Aug 19. doi:10.1038/s41598-019-48593-4 Reference #2: Takahashi S, Murata S, Yoshino Y, Kobayashi Y, Nakamura M. Gastric perforation related to concurrent use of nintedanib and ramucirumab. Respirol Case Rep. 2018;7(1):e00383. Published 2018 Nov 8. doi:10.1002/rcr2.383, Ellis LM, Hicklin DJ. VEGF-targeted therapy: mechanisms of anti-tumour activity. Nat Rev Cancer. 2008;8(8):579-91. Kamba T, Tam BY, Hashizume H, et al. VEGF-dependent plasticity of fenestrated capillaries in the normal adult microvasculature. Am J Physiol Heart Circ Physiol. 2006;290(2):H560-76. Reference #3: Liu J, Nicum S, Reichardt P, Croitoru K, et al. Assessment and management of diarrhea following VEGF receptor TKI treatment in patients with ovarian cancer. Gynecol Oncol. 2018;150(1):173-179. 6) https://apps.who.int/iris/bitstream/handle/10665/330444/WPN-2019-06-eng.pdf?ua=1 (accessed 3/13/2020) 7) https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/205832s000lbl.pdf (accessed 3/13/2020) https://apps.who.int/iris/bitstream/handle/10665/330444/WPN-2019-06-eng.pdf?ua=1 (accessed 3/13/2020) https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/205832s000lbl.pdf (accessed 3/13/2020) DISCLOSURES: Consultant relationship with Veracyte Please note: $1001 - $5000 Added 04/03/2020 by Steven Nathan, source=Web Response, value=Honoraria Consultant relationship with United Therapeutics Please note: $5001 - $20000 Added 05/27/2020 by Steven Nathan, source=Web Response, value=Consulting fee Consultant relationship with Bellerophon Please note: $5001 - $20000 Added 05/27/2020 by Steven Nathan, source=Web Response, value=Consulting fee Speaker/Speaker's Bureau relationship with Roche-Genentech Please note: $5001 - $20000 Added 05/27/2020 by Steven Nathan, source=Web Response, value=Honoraria Speaker/Speaker's Bureau relationship with Boerhinger-Ingelheim Please note: $20001 - $100000 Added 05/27/2020 by Steven Nathan, source=Web Response, value=Honoraria Consultant relationship with Boehringer Ingelheim Pharmaceuticals Please note: $1001 - $5000 Added 05/18/2020 by Vijay Ramalingam, source=Web Response, value=Honoraria No relevant relationships by Anusha Yelisetty, source=Web Response

Clinical validation demonstrates concordance of qSOFA and POC lactate Bayesian model: Results from the ACDC Phase-2 program.

We conducted a two tired validation study with one arm focusing on Bayesian modeling and a second retrospective observational arm addressing real data validation. For Bayesian modeling, sensitivity and specificity of prehospital lactate were attained from pooled meta-analysis data. Later, for clinical validation, we used data from 2016 to 2017 of ED patients diagnosed with sepsis. Pretest probabilities from qSOFA score where combined with prehospital lactate and inserted into a Bayesian model to calculate posttest probabilities. Absolute and relative diagnostic gains were calculated. Statistical significance was assessed via t-test, chi square and odds ratio. P value was set to be 0.05. For the Bayesian arm; meta-analysis data for prehospital lactate resulted in a positive likelihood ratio (LR+) of 1.69 and negative likelihood ratio (LR-) of 0.44. Integration of lactate and qSOFA demonstrated significant post-test improvements. On the Clinical Validation arm, 1470 patients were included with 176 patients meeting analysis criteria. When comparing qSOFA + Abnormal Lactate vs qSOFA and normal Lactate, the ICU vs Non-ICU cohorts were statistically different (p < 0.01) Odds Ratio: 2.35 (95% CI [1.22-4.6]). Bayesian mathematical model demonstrated that a qSOFA-based clinical decision can be complemented by the use of point of-care lactate. These results were confirmed by our clinical validation arm.

Outcomes of Adult Ewing Sarcoma Treated with Multimodality Therapy: A Single-Institute Experience

Introduction Ewing sarcoma (ES) is more common in children and relatively rare in adults. Adult ES has poor prognosis than children. Treatment approaches for adults have been extrapolated from pediatric experience. Data on adult ES are very few because of its rarity in adults. The present study was done to analyze the clinical profile and outcome of adult ES. Aims The aim was to study the clinical and pathological treatment and outcomes in adult ES. Subjects and Methods Between 2010 and 2017, a total of 73 ES patients with age more than 18 years were retrospectively analyzed. Survival analysis was done by plotting Kaplan–Meier curves. Results A total of 73 patients were diagnosed with ES during 2010 to 2017. Among them, 43 (58.9%) had localized disease with a median age of 24.5 years. Males were 44 (60.3%) and females were 29 (39.7). Pain (75.3%) was the most common symptom at presentation. Nine patients had incomplete details and were excluded from the analysis. Among 21 (28.8%) patients, the lung (61.9%) was the most common site of metastasis followed by the bone, bone marrow, and brain. The median number of chemotherapy cycles in the localized disease was 14 (range 1–17), and in metastatic disease, it was 4 (range 1–7). Univariate analysis was done with respect to age (< 25 vs. ≥25), gender, elevated or normal serum lactate dehydrogenase level, tumor size (< 8 cm versus ≥8 cm), site (axial versus extremity), and neoadjuvant chemotherapy (NACT) given or not. NACT had a significant impact on overall survival (OS) and the rest had no effect. At a median follow-up of 40 months, the 3-year OS in localized disease was 87.4%. In metastatic disease, the median OS was 13 months with 3-year OS of 26%. Conclusions Outcomes with multimodality therapy in adult ES patients with localized disease are comparable to that of a pediatric cohort. However, metastatic disease has poor survival.

S1759 Early Post-Endoscopic Transverse Colo-Colonic Intussusception

INTRODUCTION: Intussusception is a form of bowel obstruction defined as the telescoping of proximal segment of bowel into a distal segment. Intussusception in adults accounts for 5% of all cases and is usually secondary to a lead point such as a tumor or polyp. Intussusception in adults presents with vomiting, abdominal pain, hematochezia, or constipation. Cases where organic lesions act as the lead point present as a bowel obstruction. CT scan is diagnostic, which can identify location and presence of a lead point. Those with lead points can cause obstruction and ischemia- surgery is the treatment. Intussusception developing after an endoscopic procedure is extremely rare. In several cases there was a polypectomy performed and the subsequent intussusception was attributed to bowel edema acting as a lead point. All cases were treated with surgical intervention. CASE DESCRIPTION/METHODS: A 54-year-old female patient with a history of diabetes presented to the ED with worsening colicky abdominal pain starting four hours after a colonoscopy with polpectomy in the transvsere colon was performed. She also experienced red mucus in her stools. Her vital signs were within normal limits. On exam, she had a non-distended abdomen, with mild tenderness over the RUQ without any palpable masses. Her blood work was significant for a white count of 13 with a normal metabolic profile and lactate. The patient had an abdominal X- ray and CT of the abdomen which showed a transverse colo-colonic intussusception with partial obstruction. The patient was seen by the surgical team who opted for a conservative management with IV fluids and nil per os. Her symptoms rapidly improved the next day. She was started on a liquid diet which was advanced without complications. She was discharged on the third day after a normal bowel movement. An MRI two months after discharge was unremarkable. DISCUSSION: Intussusception with colonoscopy as an etiology is very uncommon. In our patient, polypectomy in the setting of colitis likely contributed to her development of an intussusception and partial bowel obstruction. There are no standard guidelines for management. In all colonoscopy-related cases cited, surgical interventions were pursued. Conservative management was pursued for our patient who had complete resolution of her symptoms. This report demonstrates that in non-malignant intussusception cases a conservative approach at first, with surgery reserved for patients with worsening symptoms, is practical.Figure 1.: Intussusception shown on abdominal CT (orange arrow).Figure 2.: Followup MRI showing resolution of intussusception (orange arrow).

ANTIPSYCHOTIC MEDICATION EFFECTS MIMICKING MYXEDEMA COMA AND SEPSIS

SESSION TITLE: Medical Student/Resident Critical Care Posters SESSION TYPE: Med Student/Res Case Rep Postr PRESENTED ON: October 18-21, 2020 INTRODUCTION: Olanzapine (Zyprexa) is an atypical antipsychotic that affects the dopaminergic pathway and is commonly used in the treatment of schizophrenia and bipolar disorder. Common side effects include extrapyramidal syndrome, akathisia, hyperprolactinemia, weight gain, and transaminitis. Rare adverse effects include hypothermia, bradycardia, and hemodynamic instability, while neutropenia is even more rare. CASE PRESENTATION: A 64-year-old woman with history of schizophrenia was brought in from jail for bilateral lower extremity edema and hypothermia unrelated to environmental exposure. On arrival, she was agitated, hypotensive (MAP <60), bradycardic (HR in 50s), and hypothermic with a rectal temperature of 90.4°F. Due to the patient’s psychotic state, no history could be elicited. Initial differential diagnoses included myxedema coma and sepsis. Fluid bolus, antibiotics, intravenous levothyroxine and hydrocortisone were immediately administered. Laboratory findings were significant for neutropenia with an absolute neutrophil count of 984, which was previously normal three weeks earlier. Peripheral smear demonstrated few large granular lymphocytes, which are normal variants. Thyroid studies showed a normal free T4 and mildly elevated TSH with a value of 6.45 mcIU/mL (0.34 – 5.60 mcIU/ml), consistent with subclinical hypothyroidism. Additional findings included a normal lactate, clear urinalysis, unremarkable chest x-ray, and pan-CT non-revealing for an infectious source. Patient did have bilateral lower extremity erythema and edema concerning for bilateral lower extremity cellulitis, but this was not significant enough to account for her severe hypothermia, bradycardia, and hemodynamic instability. On further investigation, the only medication the patient was taking at the time of presentation was olanzapine, a court-ordered medication for her psychotic symptoms, which was started thirteen days prior to symptoms. During her hospital stay, olanzapine was stopped and switched to aripiprazole (Abilify), which was tolerated well by the patient in the past. Additionally, with active warming and supportive care with fluids and antibiotics, the patient’s clinical condition improved. Neutropenia resolved five days after olanzapine was discontinued, and all culture data returned without any sign of infection. DISCUSSION: This case illustrates how rare adverse reactions from an antipsychotic medication can confound the clinical picture and mimic another diagnosis, specifically myxedema coma and sepsis. There have been less than a hundred reported cases of antipsychotic-related hypothermia and only two reported cases of olanzapine-related neutropenia in the literature. CONCLUSIONS: Awareness of these rare adverse reactions, alongside a thorough investigation and open-minded differential were critical in deciphering this intriguing case. Reference #1: Malhotra K et al. Olanzapine-induced neutropenia. Ment Ill (2015) 7(1):5871. Reference #2: Zonnenberg C et al. Hypothermia due to antipsychotic medication: a systematic review. Front Psychiatry (2017) 8:165. DISCLOSURES: No relevant relationships by Liwayway Andrade, source=Web Response No relevant relationships by Chukwufumnanya Ikeneme, source=Web Response No relevant relationships by Jaison John, source=Web Response No relevant relationships by Nisha Soneji, source=Web Response

Clinical Characteristics and Prognosis of Patients with Relapsed or Refractory Diffuse Large B-Cell Lymphoma

To investigate the clinical characteristics of relapsed or refractory (R/R) diffuse large B-cell lymphoma (DLBCL) and the factors affecting overall survival (OS) time. The clinical data of 14 R/R DLBCL patients admitted to the Hainan Hospital of Chinese PLA General Hospital from April 2012 to March 2019 were analyzed retrospectively and the overall response rate (ORR) after the end of different treatments was estimated. Kaplan-Meier method was used to describe the survival curve, and Log-rank test was used to compare whether different survival curves showed statistically different. There were 8 males and 6 females with a median age of 51 (26-75) years old and the median course of treatment before R/R was 7 (4-13). Finally, 11 patients achieved remission, 6 patients of which showed complete remission, and 5 patients showed partial remission, with the median ORR duration at 2.5 (0-51) months. All patients in the group of ibrutinib combined with second-line chemotherapy achieved remission (4/4), it was equivalent to the high-dose chemotherapy followed by autologous hematopoietic stem cell transplantation (HDC-AHSCT) group (4/4), which was significantly higher than that of the other second-line group (3/6). The median OS time of patients was 17 (6-76) months. The survival of patients receiving ibrutinib combined with second-line chemotherapy and HDC-AHSCT was significantly better than that of patients not receiving ibrutinib combined with second-line chemotherapy and HDC-AHSCT. Normal lactate dehydrogenase, IPI score＜3 at diagnosis, and CR/PR after treatment could improve the survival time of patients. The duration of remission for R/R DLBCL patients is short and the prognosis is very poor. The survival time of patients with high level of lactate dehydrogenase, IPI score≥3 at diagnosis and SD/PD after treatment is significantly shortened. Ibrutinib combined second-line chemotherapy and HDC-AHSCT can improve the efficacy and survival of R/R DLBCL patients.

Response to the Time

Response to the Time

PRIMARY MEDIASTINAL CHORIOCARCINOMA (PMC) IN A YOUNG WOMAN WITH HEMOPTYSIS AND A LUNG MASS

SESSION TITLE: Medical Student/Resident Lung Cancer Posters SESSION TYPE: Med Student/Res Case Rep Postr PRESENTED ON: October 18-21, 2020 INTRODUCTION: Primary mediastinal choriocarcinoma (PMC) is an extra gonadal, non-gestational, angioinvasive rare germ cell neoplasm that mostly arises along the midline structures. PMC contains syncytiotrophoblastic cells which secrete human chorionic gonadotropin hormone (hCG). An elevated hCG is considered an important serologic tumor marker in the diagnosis of mediastinal germ cell tumor, in the absence of gestation and with no previous gynecologic malignancy. CASE PRESENTATION: A 39 year-old woman with no past medical history was admitted to the hospital with severe right sided chest pain associated with hemoptysis that started 2 weeks prior to admission. Physical exam revealed decreased breath sounds on the right hemithorax with dullness to percussion. Bloodwork was significant for β-HCG of 6,566 mlU/ml with negative alpha fetoprotein, and normal lactate dehydrogenase. A CT scan of the chest revealed a large necrotic solid mass with numerus enlarged vessels located in the anterior mediastinum (Figure 1). PET scan was negative for any metastatic lesions. Transvaginal ultrasound was negative for intrauterine or ectopic pregnancy. Transthoracic core biopsy showed poorly differentiated choriocarcinoma. Immunohistochemistry staining was positive for β-HCG, placental alkaline phosphatase, and pancytokeratin AE1/AE3 (Figure 2). The tumor was not amenable to surgical resection due to its large size and high vascularity. The patient was started on cisplatin and etoposide followed by etoposide, MTX, Act-D, cyclophosphamide, and vincristine (EMA-CO). After the first course of chemotherapy, the levels of β-HCG markedly decreased. DISCUSSION: PMC is a rare malignancy in both genders, more prevalent in men than in women. The natural process of PMC has been poorly understood. Possible theories include: (1) trophoblastic embolus related to a gestational event after a long period of latency; (2) metastases from a primary gonadal choriocarcinoma; (3) retained primordial germ cells that migrated during embryogenesis. An extensive workup is required to exclude other β-HCG-positive tumors from PMC, such as primary poorly differentiated non-small cell carcinoma of the lung, and gestational metastatic choriocarcinoma. Our patient was found to have a large highly vascular mass in the presence of elevated β-HCG, and absence of primary genital tumor. The histological features showed extensive areas of hemorrhage and necrosis and biphasic cellular population including cytotrophoblastic and syncytiotrophoblastic cells. In contrast to gestational choriocarcinoma, PMC is rapidly progressive and fatal in the great majority of cases with a dismal 5 years survival of less than 5%. CONCLUSIONS: Due to the rarity of PMC, currently there is no consensus regarding treatment guidelines. Thus, case reports such as this contribute to the scant literature to raise the profile of this rare and devastating disease. Reference #1: Ruan Z, Wang S, Wang Z, Jing Y. A rare case of bilateral massive hemothorax from spontaneous rupture of a primary mediastinal mixed germ cell tumor. Ann Thorac Surg. 2012;93:664–666 Reference #2: Bachmann J, Ernestus K, Werner T, et al. Detection of primary choriocarcinoma in the mediastinum by F-18 FDG positron emission tomography. Clin Nucl Med. 2007;32:663–665. Reference #3: Serno J, Zeppernick F, Jakel J, Primary pulmonary choriocarcinoma; cas report and the review of the literature, Gynecologic nad obstetric investigation, vol. 74, no. 2, pp. 171-176,2012 DISCLOSURES: No relevant relationships by Marwah Abduljabbar, source=Web Response No relevant relationships by Sara Mehrsefat, source=Web Response No relevant relationships by jorge otoya, source=Web Response No relevant relationships by Noman Subhani, source=Web Response no disclosure on file for Maria Wallis-Crespo

Effects of Different Storage Media, Temperature, and Time on Osteoblast Preservation in Autogenous Bone Grafts: A Histomorphometrical Analysis.

Statement of the Problem: Autogenous bone graft is the gold standard for bone reconstruction. Osteogenic cells must be kept viable in graft for a successful procedure. In extracorporeal preservation of grafts during surgery, three different factors may influence the quality of grafts. These factors include temperature, storage medium, and time interval.Purpose: In this study, we evaluated the effects of different storage media, temperatures, and times on osteoblast count in autogenous bone grafts, preserved extracorporeally.Materials and Method: Samples were obtained from iliac crest region in a goat. The grafts were preserved in 36 groups of different storage time, temperature, and medium. Samples were histomorphometrically analyzed to determine osteoblast count as the criteria of graft quality.Results: In almost all samples, room temperature was the most and incubator was the least favorable storage temperatures. In grafts preserved in room temperature, no difference was noted between normal saline and Ringer’s lactate solution and in almost all of the samples autologous blood and dry environment were more favorable media than Ringer’s lactate solution. The effect of storage time was highly depended on the combination of temperature and solution.Conclusion: The results demonstrated that for preserving as many osteoblasts as possible in bone grafts, the best temperature was room temperature and the least favorable temperature was incubator. In addition, when bone fragments were preserved in room temperature, the best medium for graft storage was blood, which showed better results than normal saline and Ringer’s lactate solution.

Etiology and prognosis for dogs with abnormal blood glucose concentrations evaluated in an emergency room.

To determine the prevalence of glucose abnormalities in nondiabetic dogs presenting to a veterinary emergency room (ER) and their association with underlying disease processes, previous glucocorticoid administration, and overall mortality. Single-center, retrospective study from January 2013 to December 2014. University Teaching Hospital. A total of 660 dogs presenting to an ER with a blood glucose concentration measured within 6 hours of presentation. None. Medical records from dogs with a blood glucose concentration measured within 6 hours of hospital admission were reviewed. Medications administered prior to blood sampling, the presence of shock, final clinical diagnosis, and survival were recorded. Hypoglycemia and hyperglycemia were defined as a blood glucose<4.4mmol/L (80mg/dL) and>6.7mmol/L (120mg/dL), respectively. Diabetic patients were removed from analysis. Hyperglycemia was found in 40.1% of dogs, whereas hypoglycemia was present in 9.0%. Hyperglycemia was most often associated with gastrointestinal disease, trauma, neoplasia, and respiratory disease. The most common diseases associated with hypoglycemia were sepsis, gastrointestinal disease, and neoplasia. Dogs in shock or with hyperlactatemia had higher blood glucose values than dogs with normal perfusion and plasma lactate concentrations (P= 0.016 and P< 0.0001, respectively). Mortality was higher in dogs with hyperglycemia (33.2%, P= 0.03) or hypoglycemia (44.6%, P= 0.0024) compared to those with normoglycemia (24.9%). Dysglycemia in nondiabetic dogs evaluated in an ER was associated with a higher mortality rate than dogs in the same population with normoglycemia. Hyperglycemia in this population was common and may represent a stress response.

Letter. Are we moving towards direct‐to‐consumer medication?

Sir, We recently saw a patient admitted with ketoacidosis after injecting GLP-1 analogue which she was able to buy over the internet. This illustrates the serious risks of taking medication without proper medical oversight. A 37-year-old patient with no previous medical history came to hospital with history of vomiting and feeling generally unwell for four days. She had been drinking fluids, but not able to keep food down over this period. The day prior to admission she had taken a dose of semaglutide 1mg which she was able to buy online from a UK based website – this was marketed as ‘skinny pen plus’. She was dehydrated; otherwise clinical examination was unremarkable. Venous blood gas showed significant acidosis with pH of 7.22 (7.35–7.45), bicarbonate of 12.8mmol/L (22–26) and normal lactate of 1.5mmol/L (0.6–2.5). Blood glucose was 3.7mmol/L with blood ketone of 6.8mmol/L. She had mild acute kidney injury with creatinine of 79μmol/L (baseline creatinine 47μmol/L). A diagnosis of starvation ketoacidosis was made and she was treated with intravenous dextrose and crystalloids. She improved clinically and all biochemical abnormalities resolved over the next 48 hours. She was discharged and advised not to take any further doses of semaglutide. On visiting this particular website, it is surprisingly easy to buy GLP-1 analogues. The website identifies them as ‘skinny pen’ and clients are able to choose either a daily or weekly preparation based on preference and cost. After making the choice the customer is required to fill out a medical questionnaire, following which the medication arrives by post. The website mentions that ‘an experienced medical team will assess suitability for medication based on information provided and the drug is dispensed from a UK based pharmacy’. This patient did not have a phone or video consultation and did not receive any information other than the leaflet along with the drug. It is of note that GLP-1 analogues are currently not licensed in the UK as treatment for weight management. It is well known that they induce significant weight loss; however, the licence is for treatment of type 2 diabetes.1 A search of the internet revealed at least half a dozen other websites offering similar prescriptions. GLP-1 analogues commonly cause gastrointestinal side effects and in about 5% of cases this can be serious enough to discontinue the drug.2 As there is no contact with a health care professional, it is unclear how much information is given to patients buying the drug online. Clearly this patient did not know what to expect and when to seek help. It is likely that we will be encountering more of such cases with potential harm to some patients. This practice is blurring the boundary line of ‘Direct-to-Consumer Pharmaceutical Advertising’ which is common practice in the USA, but not allowed in the UK. All online pharmacies in the UK are regulated by the General Pharmaceutical Council; however, the NHS advises caution when ordering online drugs.3 Regulations about online consultations and prescriptions may need to be reviewed to ensure safe and appropriate use of GLP-1 analogues.

1082MO 5-year characterization of complete responses in patients with advanced melanoma who received nivolumab plus ipilimumab (NIVO+IPI) or NIVO alone

5-year outcomes of patients (pts) with a CR to NIVO+IPI or NIVO alone and factors associated with continued CR or relapse are unknown. The current pooled analysis addresses these key questions, including a 12-mo CR landmark analysis used to decrease the time guarantee bias. In this post hoc analysis, 5-yr data were pooled from the phase III CheckMate 066 and 067 studies and the phase II CheckMate 069 study of pts with treatment-naive, advanced melanoma. Analyzed pts received either the approved regimen of NIVO+IPI followed by NIVO monotherapy or NIVO monotherapy. Characteristics and outcomes of pts with a CR (by RECIST) were investigated, including 12-mo landmark survival analyses to determine the likelihood of being alive at 5-y among pts in CR by 12 mo (to mitigate the time guarantee bias). Minimum follow-up was 60 mo since randomization of the last pt in each study; pooled median mo of follow-up was 63 for NIVO+IPI (n=409) and 64 for NIVO (n=526). CRs were demonstrated in 96 (23%) NIVO+IPI pts and 102 (19%) NIVO pts; of CR pts alive at 5 yrs, 75/79 (95%) and 85/91 (93%) had not received subsequent systemic therapy. Baseline characteristics significantly associated with CR (Table) were M stage (NIVO+IPI), PD-L1 ≥ 5% (NIVO), normal lactate dehydrogenase (LDH; both) and fewer disease sites (both). Median duration of CR and median time to subsequent systemic therapy were not reached in either group. Median mo (Q1, Q3) to CR was 9.1 (2.8, 23.1) for NIVO+IPI and 11.8 (5.8, 26.5) for NIVO alone. In pts in CR at 12-mo, 5-y OS for NIVO+IPI and NIVO respectively was 85% and 86%; PFS was 84% and 82%. NIVO+IPI- or NIVO-treated pts in CR at 12 mo have a high likelihood of being alive at 5 y even without subsequent systemic therapy. Several baseline pt characteristics were associated with CR duration. Factors associated with CR may differ for NIVO+IPI and NIVO alone. Biomarker analyses are ongoing.Table: 1082MONIVO+IPINIVOn/NCR % (95% CI)P-valuen/NCR % (95% CI)P-valueLDH status >ULN ≤ULN16/138 80/26912 (7-18) 30 (24-36)<0.000119/191 81/31710 (6-15) 26 (21-31)<0.0001LDH status > 2xULN ≤ 2xULN2/43 94/3645 (1-16) 26 (21-31)0.00202/58 98/4503 (<1-12) 22 (18-26)0.0010M stage M0 M1A M1B M1C9/19 20/62 30/98 37/22947 (24-71) 32 (21-45) 31 (22-41) 16 (12-22)0.00048/35 15/70 30/110 49/31123 (10-40) 21 (12-33) 27 (19-37) 16 (12-20)0.0587No. lesion sites 1 2-3 >353/128 36/211 7/7041 (33-50) 17 (12-23) 10 (4-20)<0.000140/130 50/303 12/9131 (23-40) 16 (12-21) 13 (7-22)0.0007PD-L1 ≥5% <5%20/92 64/26622 (14-32) 24 (19-30)0.650742/139 58/33530 (23-39) 17 (13-22)0.0017ULN, upper limit of normal. Open table in a new tab

Normal Lactate and Unenhanced CT-Scan Result in Delayed Diagnosis of Acute Mesenteric Ischemia.

To investigate the factors associated with a delayed diagnosis (DD) of acute mesenteric ischemia (AMI). An observational cohort study from an intestinal failure center. The primary outcome was DD >24 hours. Between 2006 and 2015, 74 patients with AMI were included and 39 (53%) had a DD. Plasma lactate <2 mmol/L (odd ratio: 3.2; 95% confidence interval: 1.1-9.1; P = 0.03) and unenhanced computed tomography scan (odds ratio: 5.9; 95% confidence interval: 1.4-25.8; P = 0.01) were independently associated with DD. Suspicion of AMI should no longer be affected by normal plasma lactate levels and should prompt evaluation by a contrast-enhanced computed tomography-scan.

Real-world Outcomes of First-line Anti-PD-1 Therapy for Advanced Melanoma: A Nationwide Population-based Study.

The efficacy of anti-programmed death-1 (PD-1) monotherapy for advanced melanoma has been established, but it is unknown to what extent patients benefit in the real world. In this observational study with nationwide population-based data from the Dutch Melanoma Treatment Registry, we analyzed real-world outcomes of first-line anti-PD-1 monotherapy in advanced melanoma patients diagnosed in 2015 to 2016. Overall survival (OS) was estimated with the Kaplan-Meier method. Competing risks analysis was used to estimate probabilities for second-line treatment, with death as competing risk. With a Cox model, the association of factors with OS was estimated. Patients who received anti-PD-1 monotherapy (n=550) had a median age of 65 years and 502 (95%) patients had an Eastern Cooperative Oncology Group performance status (ECOG PS) of 0-1, 383 (70%) had normal lactate dehydrogenase (LDH), 370 (67%) had stage IV-M1c disease, and in 441 (81%), brain metastases were absent. The median OS was 24 months [95% confidence interval (CI): 20-30 mo]. The median OS of patients normally eligible for phase III trial participation was 31 months (95% CI: 23-not estimable). The BRAF mutation was associated with superior OS. ECOG PS of ≥1, symptomatic brain metastases, and liver metastases were associated with inferior OS and, together with elevated LDH, with death before second-line treatment. Patients with a complete response had a 2-year OS probability from first reported complete response of 92% (95% CI: 86%-99%). Real-world advanced melanoma patients in the Netherlands have benefitted from anti-PD-1 monotherapy. ECOG PS ≥1, symptomatic brain metastasis, liver metastasis, and elevated LDH are important prognostic factors for survival. The additional information that this study provides could help to improve more effective use in the real world.

What’s Your Motivation?

What’s Your Motivation?

DIABETIC KETOACIDOSIS WITH LOWER-THAN-ANTICIPATED GLUCOSE LEVELS WITH SGLT-2 INHIBITOR CANAGLIFLOZIN: A CASE REPORT AND REVIEW OF THE LITERATURE.

We describe a case report of a patient who presented with euglycemic diabetic ketoacidosis (euDKA), six days after starting treatment with sodium-glucose cotransporter-2 (SGLT2) inhibitor, Canagliflozin. ‘Euglycemic diabetic ketoacidosis’ or ‘DKA with lower-than-anticipated glucose levels’ (as recommended by AACE/ACE) is a rare, challenging and easy to miss the diagnosis A 41-year-old male with a history of type 2 Diabetes Mellitus presented with uncontrolled hyperglycemia. Canagliflozin (SGLT2 inhibitor) was added to his anti-diabetic regimen of Metformin and Sitagliptin. Six days later, he presented with symptoms of diabetic ketoacidosis with normal blood glucose of 131mg/dl. The patient was further investigated with arterial blood gas analysis and serum ketone studies, keeping in view of the potential of euglycemic diabetic ketoacidosis (euDKA) with SGLT2 inhibitor use. The clinical picture and lab values of the patient were consistent with diabetic ketoacidosis(DKA), although it is rare in type 2 DM. Blood glucose was in the normal range which could have delayed the diagnosis if the physician was not vigilant. If one had only focused on the blood glucose, then this potentially fatal condition could have been missed. However, when other causes of anion gap metabolic acidosis were excluded and the lab values of urine ketones, elevated beta-hydroxybutyrate, reduced bicarbonate, and normal lactate interpreted, it leads to the diagnosis of SGLT2 inhibitor-associated euglycemic DKA. We performed a literature review of this topic and discuss the history of euglycemic diabetic ketoacidosis, risk factors, pathophysiology, diagnosis, management, and prevention of SGLT2 inhibitor-induced euDKA.

Brain Tissue Oxygen Response as Indicator for Cerebral Lactate Levels in Aneurysmal Subarachnoid Hemorrhage Patients.

Early detection of cerebral ischemia and metabolic crisis is crucial in critically ill subarachnoid hemorrhage (SAH) patients. Variable increases in brain tissue oxygen tension (PbtO2) are observed when the fraction of inspired oxygen (FiO2) is increased to 1.0. The aim of this prospective study was to evaluate whether a 3-minute hyperoxic challenge can identify patients at risk for cerebral ischemia detected by cerebral microdialysis. Twenty consecutive severe SAH patients undergoing continuous cerebral PbtO2 and microdialysis monitoring were included. FiO2 was increased to 1.0 for 3 minutes (the FiO2 challenge) twice a day and PbtO2 responses during the FiO2 challenges were related to cerebral microdialysis-measures, ie, lactate, the lactate-pyruvate ratio, and glycerol. Multivariable linear and logistic regression models were created for each outcome parameter. After predefined exclusions, 274 of 400 FiO2 challenges were included in the analysis. Lower absolute increases in PbtO2 (∆PbtO2) during FiO2 challenges were significantly associated with higher cerebral lactate concentration (P<0.001), and patients were at higher risk for ischemic lactate levels >4 mmol/L (odds ratio 0.947; P=0.04). Median (interquartile range) ∆PbtO2 was 7.1 (4.6 to 12.17) mm Hg when cerebral lactate was >4 mmol/L and 10.2 (15.76 to 14.24) mm Hg at normal lactate values (≤4 mmol/L). Median ∆PbtO2 was significantly lower during hypoxic than during hyperglycolytic lactate elevations (4.6 vs. 10.6 mm Hg, respectively; P<0.001). Lactate-pyruvate ratio and glycerol levels were mainly determined by baseline characteristics. A 3-minute FiO2 challenge is an easy to perform and feasible bedside diagnostic tool in SAH patients. The absolute increase in PbtO2 during the FiO2 challenge might be a useful surrogate marker to estimate cerebral lactate concentrations and might be used to identify patients at risk for impending ischemia.